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Modulation of Integrin ₄β₁ (VLA-4) in Dry Eye Disease

Tatiana Ecoiffier, MS, MEng; Jaafar El Annan, MD; Saadia Rashid, MD; Debra Schaumberg, ScD, OD, MPH; Reza Dana, MD, MSc, MPH

Arch Ophthalmol. 2008;126(12):1695-1699.

Objective  To study the effect of topical application of very late antigen 4 (VLA-4) small-molecule antagonist (anti–VLA-4 sm) in a mouse model of dry eye disease.

Methods  Anti–VLA-4 sm (or control vehicle) was applied topically to mice placed in a controlled-environment chamber. Corneal fluorescein staining and conjunctival T-cell enumeration were performed in the different treatment groups. Real-time polymerase chain reaction was used to quantify expression of inflammatory cytokines in the cornea and conjunctiva.

Results  Dry eye syndrome induced increased corneal fluorescein staining, corneal and conjunctival tumor necrosis factor messenger RNA expression, and T-cell infiltration into the conjunctiva. Very late antigen 4 blockade significantly decreased corneal fluorescein staining compared with the untreated dry eye disease and control vehicle–treated groups (P < .001 and P = .02, respectively). In addition, VLA-4 blockade was associated with a significant decrease in conjunctival T-cell numbers (P < .001 vs control vehicle–treated group) and tumor necrosis factor- transcript levels in the cornea (P = .04 vs control vehicle–treated group) and conjunctiva (P = .048 vs control vehicle–treated group).

Conclusion  Application of topical anti–VLA-4 sm led to a significant decrease in dry eye signs and suppression of inflammatory changes at the cellular and molecular levels.

Clinical Relevance  Topical blockade of VLA-4 may be a novel therapeutic approach to treat the clinical signs and inflammatory changes accompanying dry eye disease.

Author Affiliations: Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School (Ms Ecoiffier and Drs El Annan, Rashid, Schaumberg, and Dana), Division of Ophthalmic Epidemiology, Brigham and Women's Hospital (Dr Schaumberg), and Massachusetts Eye and Ear Infirmary (Dr Dana), Boston.

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